The Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, IL 60637 USA ; The Committee on Cancer Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637 USA.
The Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, Chicago, IL 60637 USA ; The Committee on Molecular Metabolism & Nutrition, 929 East 57th Street, Chicago, IL 60637 USA.
Cancer Metab. 2015 Mar 26;3:4. doi: 10.1186/s40170-015-0130-8. eCollection 2015.
Mitophagy is a selective form of macro-autophagy in which mitochondria are selectively targeted for degradation in autophagolysosomes. Mitophagy can have the beneficial effect of eliminating old and/or damaged mitochondria, thus maintaining the integrity of the mitochondrial pool. However, mitophagy is not only limited to the turnover of dysfunctional mitochondria but also promotes reduction of overall mitochondrial mass in response to certain stresses, such as hypoxia and nutrient starvation. This prevents generation of reactive oxygen species and conserves valuable nutrients (such as oxygen) from being consumed inefficiently, thereby promoting cellular survival under conditions of energetic stress. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses has been implicated both positively and negatively in tumorigenesis, while the potential of targeting mitophagy specifically as opposed to autophagy in general as a therapeutic strategy remains to be explored. The challenges and opportunities that come with our heightened understanding of the role of mitophagy in cancer are reviewed here.
自噬是一种选择性的巨自噬形式，在此过程中，线粒体被选择性地靶向到自噬溶酶体中进行降解。自噬可以产生有益的效果，即消除旧的和/或受损的线粒体，从而保持线粒体池的完整性。然而，自噬不仅限于功能失调的线粒体的周转率，而且还会在受到某些应激（如缺氧和营养饥饿）时促进整体线粒体质量的减少。这可以防止活性氧的产生，并节省宝贵的营养物质（如氧气），避免其低效消耗，从而促进在能量应激条件下细胞的存活。在应对致癌应激时，无法适当地调节线粒体周转率，这既可以正面也可以负面地影响肿瘤发生，而将靶向自噬作为一种治疗策略的潜在性，与普遍靶向自噬相比，仍有待探索。本文综述了自噬在癌症中的作用所带来的挑战和机遇。
